Human GeneticsConcepts and Applications

Ninth Edition

RICKI LEWIS

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

PowerPoint® Lecture Outlines Prepared by Johnny El-Rady, University of South Florida

4 Single-Gene Inheritance

2

A Tale of Two Families

Modes of inheritance are the patterns in which single-gene traits and disorders occur in families

Huntington disease is autosomal dominant

- Affects both sexes and typically appears every generation

Cystic fibrosis is autosomal recessive

- Affects both sexes and can skip generations through carriers

3

Figure 3.2

Family with Huntington Disease

Figure 4.1

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Figure 3.2

Treating Cystic Fibrosis

Figure 4.2

5

Gregor Mendel

A priest who performed research in plant breeding

Without knowledge of DNA, cells, or chromosomes

Described the units of inheritance and how they pass from generation to generation

Not recognized during his lifetime

6

Gregor Mendel

Experimented from 1857-1863 on traits in 24,034 plants

Developed the laws of inheritance

Used:- Controlled plant breeding- Careful recordkeeping - Large numbers- Statistics

7Figure 4.2

Mendel Studied Transmission of Seven Traits in the Pea Plant

Figure 4.3

8

True-Breeding Plants

Offspring have the same trait as parent

Examples:

- Round-seeded parents produce all round-seeded offspring

- Yellow-seeded parents produce all yellow-seeded offspring

- Short parents produce all short offspring

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Monohybrid Cross

True-breeding plants with two forms of a single trait are crossed

Progeny show only one form of the trait

The observed trait is dominant

The masked trait is recessive

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Monohybrid Cross

Parental generation (P1)

Tall X Short

F1

All Tall

F2

1/4 Short : 3/4 TallFigure 4.3

Figure 4.4

11

Monohybrid Cross

In these experiments, Mendel confirmed that hybrids hide one expression of a trait, which reappears when hybrids are crossed

Mendel speculated that gametes contained particulate units or “elementen”

These are now called alleles

- Versions of the same gene

- Differ in DNA sequence at one or more sites

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Mendel's First Law – Segregation

Each plant possesses two units (alleles) for each trait

Alleles separate in the formation of gametes

Gametes contain ONE allele for each trait

At fertilization, gametes combine at random

Note: Mendel was really observing the events of meiosis and fertilization

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Mendel's First Law – Segregation

Figure 4.5

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Mendel's Data

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Terms

Genotype = The alleles present in an individual

- Homozygous carry same alleles TT or tt

- Heterozygous carry different alleles Tt

Phenotype = The trait observed

- Tall or Short

Wild Type = Most common phenotype

Mutant phenotype = A product of a change in the DNA

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Punnett SquareRepresents particular genes in gametes and

how they may combine in offspring

Figure 4.6

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Test Cross

A monohybrid cross yields:

a 1 TT : 2 Tt : 1 tt genotypic ratio, and

a 3 tall : 1 short phenotypic ratio

Mendel distinguished the TT from Tt tall plants with a test-cross

- Cross an individual of unknown genotype with a homozygous recessive individual

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Test Cross

Figure 4.7

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Eye Color

Wild-type human eye color is brown

- Blue and green eyes stemmed from mutations or SNPs that persisted

The surface of the back of the iris contributes to the intensity of eye color

Figure 4.8

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Autosomal Inheritance

Human autosomal traits are located on the non-sex chromosomes (#s 1-22)

They may be inherited as:

- Autosomal dominant or

- Autosomal recessive

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Autosomal Dominant Traits

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For many autosomal dominant traits, affected individuals are heterozygous (Aa)

- The homozygous dominant phenotype (AA) is either lethal or very rare

Figure 4.9

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Autosomal Recessive Traits

5. More likely to occur in families with consanguinity

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Autosomal Recessive Traits

Figure 4.10

25Reading 4.1, Figure 1

Inheritance of Some Common Traits

Box, Figure 1

26

Solving Genetic Problems

Follow these five general steps:

1) List all genotypes and phenotypes for the trait

2) Determine the genotypes of the parents

3) Derive possible gametes

4) Unite gametes in all combinations to reveal all possible genotypes

5) Repeat for successive generations

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Whether an allele is dominant or recessive is important in determining risk and critical in medical genetics

Reflect the characteristics or abundance of a protein

Recessive traits have “loss of function”

Dominant traits have “gain of function”

Recessive disorders tend to be more severe

On the Meaning of Dominance and Recessiveness

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Mendel's Second Law – Independent Assortment

Considers two genes on different chromosomes

The inheritance of one does not influence the chance of inheriting the other

Independent assortment results from the random alignment of chromosome pairs during metaphase I of meiosis

29Figure 4.9

Mendel's Second Law – Independent Assortment

Figure 4.11

30Figure 4.9

Mendel's Second Law – Independent Assortment

Figure 4.12

31

Trihybrid Cross and forked line method

It is much less difficult to consider each contrasting pair of traits separately than to combine these results. Thus the forked line method can be used to determine gametes

Do Forked line method on the following Problems: AaBbCc AaBBCc

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Gametes and zygotes combinations

# of prs of heterozygous genes

# of gamete genotypes

# progeny phenotypes

# progeny phenotypes

# possible combinatons of gametes

1 2 2 3 4

2 4 4 9 16

3 8 8 27 64

4 16 16 81 256

n 2n 2n 3n 4n

33

Probability

The likelihood that an event will occur

Two applications of probability theory are useful in solving genetics problems

1) Product rule

2) Sum rule

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Product Rule

The probability of simultaneous independent events equals the product of their individual probabilities

Example:

- If both parents are dihybrid (RrYy), what is the probability of having an offspring that is homozygous recessive for both traits?

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Product Rule

Do the reasoning for one gene at a time, then multiply the results

Figure 4.13

36

Using Probability to Track Three Traits

Figure 4.14

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Sum Rule

The probability of mutually exclusive events equals the sum of the individual probabilities

Example:

- Parents are heterozygous for a trait, R.

- What is the chance that their child carries at least one dominant R allele?

- Probability of child being RR = 1/4

- Probability of child being Rr = 1/2

- Probability of child being R_ = 1/4 + 1/2 = 3/4

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Pedigree Analysis

For researchers, families are tools; the bigger the family, the easier it is to discern modes of inheritance

Pedigrees are symbolic representations of family relationships and the transmission of inherited traits

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Pedigree AnalysisFigure 4.15

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An Unusual Pedigree

A partial pedigree of Egypt’s Ptolemy Dynasty showing:

- Genealogy not traits

- Extensive inbreeding

Figure 4.16a

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Autosomal Dominant Trait

Polydactyly = Extra fingers and/or toes

Figure 4.16b

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Autosomal Recessive Trait

Albinism = Deficiency in melanin production

Figure 4.17

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An Inconclusive Pedigree

This pedigree can account for either an autosomal dominant or an autosomal recessive trait

Figure 4.18

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Conditional Probability

Pedigrees and Punnett squares apply Mendel’s laws to predict the recurrence risks of inherited conditions

Example:

- Taneesha’s brother Deshawn has sickle cell anemia, an autosomal recessive disease.

- What is the probability that Taneesha’s child inherits the sickle cell anemia allele from her?

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Taneesha and Deshawn’s parents must be heterozygous

Taneesha is not affected and cannot be ss

Probability Taneesha is a carrier = 2/3Probability child inherits sickle cell allele = 1/2 Probability child carries sickle cell allele from her

= 2/3 x 1/2 = 1/3

X

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